Embryo implantation is essential to the successful establishment of pregnancy. A previous study has demonstrated that actinomycin D (ActD) could initiate the activation of mouse delayed implantation. However, the mechanism underlying this activation remains to be elucidated. A low dose of ActD is an inducer of nucleolar stress. This study was to examine whether nucleolar stress is involved in embryo implantation. We showed that nucleolar stress occurred when delayed implantation was activated by ActD in mice. ActD treatment also stimulated the Lif-STAT3 pathway. During early pregnancy, nucleolar stress was detected in the luminal epithelial cells during the receptive phase. Blastocyst-derived lactate could induce nucleolar stress in cultured luminal epithelial cells. The inhibition of nucleophosmin1 (NPM1), which was a marker of nucleolar stress, compromised uterine receptivity and decreased the implantation rates in pregnant mice. To translate these mouse data into humans, we examined nucleolar stress in human endometrium. Our data demonstrated that ActD-induced nucleolar stress had positive effects on the embryo attachment by upregulating IL32 expression in non-receptive epithelial cells rather than receptive epithelial cells. Our data should be the first to demonstrate that nucleolar stress is present during early pregnancy and is able to induce embryo implantation in both mice and humans.

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A better understanding of willingness to separate waste and waste separation behaviour can aid the design and improvement of waste management policies. Based on the intercept questionnaire survey data of undergraduate students and residents in Zhengzhou City of China, this article compared factors affecting the willingness and behaviour of students and residents to participate in waste separation using two binary logistic regression models. Improvement opportunities for waste separation were also discussed. Binary logistic regression results indicate that knowledge of and attitude to waste separation and acceptance of waste education significantly affect the willingness of undergraduate students to separate waste, and demographic factors, such as gender, age, education level, and income, significantly affect the willingness of residents to do so. Presence of waste-specific bins and attitude to waste separation are drivers of waste separation behaviour for both students and residents. Improved education about waste separation and facilities are effective to stimulate waste separation, and charging on unsorted waste may be an effective way to improve it in Zhengzhou.

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Pregnancy is accompanied by significant physiological changes that might affect the in vivo drug disposition. Olanzapine is prescribed to pregnant women with schizophrenia, while its pharmacokinetics during pregnancy remains unclear. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of olanzapine in the pregnant population. With the contributions of each clearance pathway determined beforehand, a full PBPK model was developed and validated in the non-pregnant population. This model was then extrapolated to predict steady-state pharmacokinetics in the three trimesters of pregnancy by introducing gestation-related alterations. The model adequately simulated the reported time-concentration curves. The geometric mean fold error of Cmax and AUC was 1.14 and 1.09, respectively. The model predicted that under 10 mg daily dose, the systematic exposure of olanzapine had minor changes (less than 28%) throughout pregnancy. We proposed that the reduction in cytochrome P4501A2 activity is counteracted by the induction of other enzymes, especially glucuronyltransferase1A4. In conclusion, the PBPK model simulations suggest that, at least at the tested stages of pregnancy, dose adjustment of olanzapine can hardly be recommended for pregnant women if effective treatment was achieved before the onset of pregnancy and if fetal toxicity can be ruled out.